As an agent for reducing the level of blood cholesterol which causes arteriosclerosis, an agent which inhibits the absorption of bile acid by capturing it such as cholestyramine and cholestipol (U.S. Pat. No. 4,027,009), an agent which inhibits the absorption of cholesterol via an intestinal tract by inhibiting an acyl coenzyme A cholesterol acyl transferase (ACAT) such as melinamide (French Patent 1476569) and a cholesterol synthesis inhibitor, especially an agent which inhibits 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase such as lovastatin (U.S. Pat. No. 4,231,938), simvastatin (U.S. Pat. No. 4,444,784) and pravastatin (U.S. Pat. No. 4,346,227) are employed in pharmaceuticals.
However, an HMG-CoA reductase inhibitor may cause a problem associated with side effects due to its inhibitory effect not only on cholesterol biosynthesis but also on a biologically essential component such as ubiquinone, dolichol and hem A.
Acute coronary artery syndrome (for example, unstable angina, acute myocardial infarction and ischemic sudden death) is caused by the destruction of a coronary artery plaque (atheroma) followed by the formation of a thrombus and the resultant plugging of the lumen of the coronary artery. Peripheral artery occlusion is caused by the destruction of an artery plaque (atheroma) followed by the formation of a thrombus and the resultant plugging of the lumen of a peripheral artery. These diseases are related closely with the characteristics of the plaque, and a lipid-rich plaque formed by the deposition of a macrophage retaining lipids such as cholesterol extensively onto an inner wall of a blood vessel is believed to cause acute coronary artery syndrome and peripheral artery occlusion.
Accordingly, the regression and removal of a lipid-rich plaque are very important for preventing or treating acute coronary artery syndrome such as acute myocardial infarction and unstable angina as well as peripheral artery occlusion. Also since a lipid-rich plaque is observed in a human whose blood cholesterol level is not high and a lipid-rich plaque once formed is difficult to be removed, an agent capable of regressing such a lipid-rich plaque efficiently has been desired. Since a lipid-rich plaque is observed in a human whose blood cholesterol level is not high, the ACAT inhibition to reduce the intestinal absorption of cholesterol is not considered to be sufficient for regressing and removing the lipid-rich plaque.